Third COVID vaccine doses raises seroconversion in patients receiving mycophenolate mofetil

April 21, 2022

2 min read


This study was funded by ZonMw. Weiske reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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Patients receiving mycophenolate mofetil combination therapies saw increased seroconversion after a third dose of SARS-CoV-2 vaccine, while patients on anti-CD20 and S1P modulators saw little impact from a third dose, noted researchers.

“Since the start of vaccination against SARS-CoV-2, concerns have been raised about the efficacy of vaccines in patients treated with immunosuppressants,” Luuk Wieske, MD, PhD, of Amsterdam University, and colleagues wrote in The Lancet Rheumatology. Several immunosuppressants used in immune-mediated inflammatory disorders have been associated with impaired seroconversion rates after SARS-CoV-2 vaccination, most notably anti-CD20 therapies, sphingosine 1-phosphate receptor (S1P) modulators, and mycophenolate mofetil.”

Title: Increases in seroconversion among patients undergoing immunotherapy after a third COVID-19 vaccine dose: Variable A: Anti-CD20 therapy; 36.8% to 45.6% Variable B: S1P modulators; 35.5% to 48.4% Variable C: Mycophenolate mofetil combination treatments; 52.5% to 89.5%
Patients receiving mycophenolate mofetil combination therapies saw increased seroconversion after a third COVID-19 vaccine dose, while patients on anti-CD20 and S1P modulators saw little impact from a third dose, according to data derived from Wieske L, et al. Lancet Rheumatol. 2022 ;doi:10.1016/S2665-9913(22)00034-0.

To investigate humoral responses following SARS-CoV-2 vaccination in the presence of various immunosuppressant therapies, Wieske and colleagues conducted a cohort study of participants treated in outpatient clinics throughout the Netherlands. The researchers additionally included patients from two national cohort studies on COVID-19 disease severity. Eligible patients were aged older than 18 years and had any immune-mediated inflammatory disorders. Pregnant patients and those undergoing concomitant treatment with immunosuppressants were excluded.

Investigators collected clinical data via online questionnaires to patients, while patients collected their own serum samples by using finger prick sets or by venipuncture. Samples were collected at baseline, 28 days after the first vaccination dose and 28 days after the second vaccination dose. For the third dose, samples were collected on the day of vaccination, 7 days post-vaccination and 28 days post-vaccination.

The analysis included 2,339 patients, including 1,869 with no previous COVID-19 infection. In all, 1,692 patients were on immunosuppressant therapies, including 1,273 on monotherapy treatment and 419 on combination regimens. Meanwhile, the control group included 473 patients with immune-mediated inflammatory disorders not receiving immunosuppressants and 174 healthy controls.

According to the researchers, the relative risk for seroconversion among patients on anti-CD20 therapy following standard vaccination was 0.32 (95% CI, 0.19-0.49). Anti-CD20 was associated with reduced anti-RBD lgG titers. For patients receiving S1P modulators , the RR for seroconversion was 0.35 (95% CI, 0.21-0.55). In those receiving mycophenolate mofetil in combination with corticosteroids, the RR for seroconversion was 0.61 (95% CI, 0.4-0.9). Patients with previous infection demonstrated boosted responses regardless of immunosuppressive therapy, the researchers wrote.

A third dose of COVID-19 vaccine increased seroconversion in patients undergoing mycophenolate mofetil combination therapies from 52.5% to 89.5%. Patients receiving S1P modulators and anti-CD20 did not demonstrate similarly significant increases — from 35.5% to 48.4% and from 36.8% to 45.6%, respectively. Meanwhile, most other immunosuppressant groups demonstrated moderately reduced titres following standard vaccination that did not increase after a third dose. However, seroconversion rates and neutralization capacity in these groups were unaffected.

“As neutralization capacity and recall responses are preserved in patients showing optimal seroconversion rates after vaccination, the lower titers are not likely to translate in loss of (short-term) protection,” Wieske and colleagues wrote. “Patients on mycophenolate mofetil combination treatments, anti-CD20 therapy, and S1P modulators showed poor humoral responses after standard vaccination regimens, and a third vaccination increased seroconversion for those taking mycophenolate mofetil combination treatments, whereas effects for those on anti-CD20 therapy and S1P modulators were limited.”

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